– Dr. med. Heinrich Kremer, of Barcelona, Spain (retired)
The devastating effects of the drug Ritalin and the long-term side effects in the brain
The number of Ritalin prescriptions for children and teens has risen twenty times within the last 8 years. These horrifying numbers point to a more than thoughtless dealing with the drug Ritalin by the medical profession.
“Raum & Zeit” (“Space & Time”) therefore, asked the longtime medical director, Dr. Med. Heinrich Kremer of the Niedersachsen and Schleswig-Holstein clinic, specializing in medications of the states Berlin, Bremen, Hamburg, to describe in detail the effects of the drug Ritalin in the brain and to introduce alternative, Ritalin-free therapies for restless children. No conscientious doctor will prescribe Ritalin after studying this article.
For the current discussion about medicating children and teens with psycho-social problems with the psycho stimulant Ritalin, biochemical label methylphenidat] Space & Time published three important articles [Barbara Simonson: “Ritalin-Children Treated with Drugs. The Dangerous Effects of the Psychopharmaca Ritalin”; Space & Time no. 111/2001; Horst Wimmer :”Ritalin and Criminality, Summons for Working Together. Space & Time no. 113/2001; Dr. med. Hedwig Vogl; “Ritalin-Are There Alternatives?” Space & Time no. 13/2001].
Legal Drug Trade
The increase of medically prescribed daily doses of Ritalin, during the time period between 1991 thru 1999, has risen 20 times. In the ranking order of prescriptions of all prescribed medications within Germany, Ritalin has climbed in rank from number 2,230 in 1991 to number 213 in 1999 (see graph 1). This development is even more disquieting since Ritalin prescriptions fall under the narcotics legislation and can only be prescribed when warranted with strict medical indicators. (3 copies have to be sent to the government narcotics department).
The upper prescription doses for Ritalin has been determined by law as 1.5g for 30 days, corresponding to an average daily doses of 50 mg. Psychiatrically, the daily doses recommended can be up to 60 mg: [See Poser, W., Ebert, U.:ZNS -Pharmaceuticals. In: Frohlich, J.C., Kirsch, W.: Practical Pharma Therapy, Springer Publisher, Berlin-Heidelberg 2000]. The currently published data of the government narcotics department shows that Ritalin consumption rose from 34 kg in 1993 to 119 kg in 1997.
The data of the pharmaceutical index of the legal medical insurance companies, excluded are private insurance companies and prescriptions in clinics, show that the daily Ritalin prescriptions almost doubled within one year from 4.7 million in 1998 to 8.4 million daily doses in 1999.The current discussion in Space & Time , in regards to the development of a legal narcotics market, due to medical prescriptions in Germany which are contrary to the intentions of the law, seems to be totally justified.
The next question of how Ritalin prescriptions are distributed in regards to children, teenagers, and adults and the regional concentrations, cannot be answered in lieu of the publicized data. There is no personal data in regards to a person’s age and gender, which could, for example, be drawn from anonymous health insurance companies. This seems to be a serious omission for all involved in public health services.
Too Many or Too Few Ritalin Prescriptions?
In the German medical publication [editor: Bundesaerztekammer and Kassenaerztliche Bundesvereinigung, corresponds to AMA], Prof. Lehmkuhl and his colleagues from the clinic and polyclinic for psychiatry and psychotherapy for children and teens at the University Koeln, were opposed to the terms, “correct use or misapplication”, and that the medical diagnoses for Ritalin prescription was issued too often. [Schubert, I. et. al., methylphenidate with hyperactive disturbances. Decrees during the 90’s. – German Medical Publication 2001; 98 A541-544, pamphlet 9.
The authors discussed the development of Ritalin usage in Germany for the 90’s exclusively in lieu of data for medically diagnosed frequency of hyperactive disturbances during childhood and teenage years. Attentions turn to obvious uncommon active behavior and the accompanying disturbances, such as attention deficit, learning difficulties and social behavior. Ritalin therapy “seems designated when the hyperactive symptoms are very visible and therefore could be dangerous for the further development of the child and also when the symptoms cannot be sufficiently decreased via other means and forms of therapy’ [Schubert, I. et.al., a.a.O.].
Since the authors do not discuss the possible origins of hyperactive disturbances during childhood and teenage years, this definition shows the subjective judgment of the prescribing doctors for Ritalin medication, as there are no objective lab diagnostics available or psychological differentiating tests.
Instead, the Koeln psychiatrist for children point to the fact that the European guidelines, and those of the German Association for Children and Teen Psychiatry, together with the professional unions for children and teen psychiatry, recommend a multi-level therapy with the inclusion of stimulants and therapeutic behavior intervention for ADHD. [Schubert, I., a.a.O.]. ADHD=Attention Deficit Hyperactivity Disorder is the English definition for the German definition ADS=Attention Deficit Syndrome, with or without hyperactive disturbances.
Therefore, Prof. Lehmkuhl and his colleagues deduce from the global data of medically prescribed Ritalin use, a ‘conservative estimation’ of 41,791 long-term Ritalin prescriptions in Germany for the year 1999. Yet, they do point out with prudence, that “the number of children who came in contact with methylphenidate (Ritalin), could possibly be much higher” [Schubert,I. et. al , a.a.O.].
The Symptoms of Nerve Messenger Material in the Brain
The essay of Barbara Simonson, Space & Time no 111/2001, cites from the medication usage instructions of Ritalin manufacturer, the Swiss pharmaceutical company, Ciba-Geigy [now Novartis]: “Ritalin is a mild stimulant for the central nervous system. The way Ritalin works in the human body is not yet quite understood, but Ritalin presumably activates the brain stem and the cortex in order to achieve a stimulating effect. There is no specific proof that could ascertain the mechanisms of how Ritalin produces mental and behavioral effects in children, nor is there convincing proof of how these effects are related to the central nervous system.”
This claim, in regards to how Ritalin works on the molecular level, is grossly misleading and the conclusion of Barbara Simonson, “The way methylphenidate works is still not established”, is incorrect. In reality, in the arena of the psycho pharmaceuticals, there are no substances that have been so well documented as amphetamines and their derivatives, Ritalin belonging to this family.
Almost all psycho-pharmaceuticals used today to influence the biochemical and bio-energetic processes in the central nervous system, act to inhibit or reinforce the interaction between messenger material, which a stimulated nerve cell delivers as a sender, and membrane molecules of a second nerve cell, which, as the receptor, transforms this biochemical message into impulses for its own stimulation.
For a long time it was assumed that the bioelectrical energy potential between two neurons in the brain would jump like a spark from nerve cell to nerve cell. A hundred years ago, the famous Spanish neurologist Santiago Ramon y Cajal nevertheless recognized that the cable-like branches of the neurons, called axions, end at certain points which separates one neuron from the others. Later, investigation could prove without a doubt that these contact points, which were called synapses [Greek synopsis=connection], consist of the end of a nerve fiber, pre-synoptic membrane, a piece of membrane of a second nerve cell, the membrane of the cell body of a branch of this neuron, and a tiny split between the two contacting nerve cell membranes, the synaptic split.
Within the pre-synoptic nerve ending, an incoming impulse releases the biochemical transmitters (neurotransmitter). It then spreads through the synaptic split and makes contact with the receptive molecules of the receptors, or, within the membrane of the adjacent nerve cell, (post-synaptic membrane). The receptors are either directly coupled with an ionic channel for incoming or outgoing sodium-potassium chloride, or they exchange with molecules within the post-synaptic membrane. These influence, via a signal relay of special molecules (second messengers), the incoming and outgoing of ions through membrane channels at more distant regions of the post – synaptic membrane. These transfer paths of signals are of special interest here for understanding the effects of amphetamines.
The respective, specific neurotransmitter of a pre-synaptic nerve cell accelerates or de-accelerates the impulse rate of the electrical energy with which the post-synaptic neuron “fires”.
The intervals between the rounds of impulses of the neuron become shorter or longer and, due to these interactions, the neurotransmissions can be stimulating or hampering. The brain houses more than ten billion neurons (together with the more than 100 million glia cells in the brain which are not neurons, but offer nutritional and immune system support). Nevertheless, each neuron synthesizes its own neurotransmitter. But many neurons form thousands of branches of their own axion, as thousands of cell branches sprout (dendrites, Greek: dendron=tree) from their cell bodies. The axions and dendrites of a single neuron are in contact with a vast number of axions and dendrites of other neurons which can be stimulated or suppressed via their synapses under the influence of different neurotransmitters.
Every Manipulation is With Risk
This immensely complex symphony of the interplay of neurotransmitters, receptors, ionic channels, signal pathways, opening of cell energy, and numerous biosyntheses between and within the totality of neurons and the cell partners, naturally has limits for understanding in the field of research. The complexity of the effect of the exchange of neurons makes us realize how risky every manipulation in the neurotransmitter arena can be when foreign substances are introduced in the brain. For every desired inhibiting or accelerating neurotransmitter function, an inhibiting or accelerating effect on other neurotransmitters, either directly or indirectly, is produced at the same time. The desired influencing of neurotransmitter function can change with long term medication, e.g. the post-synaptic characteristics, and thus, can increase the original symptoms, and in some cases can make them irreversible. We cannot maintain that the molecular interactions are identical with psychological processes.
Meanwhile, more than 50 neurotransmitters of the central nervous system are known. The speculation is that there could be up to 200 different neurotransmitters. Half a dozen of the ‘classical’ neurotransmitters were discovered before 1975, the majority was discovered only during the last 25 years. [A selection of these messengers in the central nervous system and its receptor partners , as well as the effects on the ionic in and output and the two signal pathways of the second messenger].
The Deception and Confusion of Amphetamine Misuse
Nerve cell material consists of simple biochemical building blocks which can be found within and outside the body cells. There is nothing mysterious about that. It mostly has to do with amino acids, short chains of amino acids [oligopeptides], or amino acids which are transformed step by step through enzymes for neurotransmitter tasks. Two of these later ones are tryptophan and tyrosin. The ‘classical’ neurotransmitter, serotonin, is synthesized from the first one and from the last, the ‘classical’ neurotransmitters dopamine noradrenalinand adrenalin are formed through a step by step enzymatic reaction.
Adrenalin was the first nerve cell messenger discovered in the adrenals as a hormone [lat. ad ren = on the kidneys] which pours into the bloodstream as a reaction to acute stress. Adrenalin is also synthesized in nerve cells of the medulla oblongata for different tasks, but is of no importance for the central nervous system in contrast to the autonomous nervous system.
Adrenalin accelerates the heartbeat in mammals and humans in critical situations, as in fight or flight predicaments, and it improves muscle power and dilates the respiratory ducts of the lungs. The latter characteristic was exploited and used as a therapeutic means for asthmatics and, with that, the story of deception and confusion in the development of amphetamines and derivatives like Ritalin, and the misuse of these substances as central stimulants, begins.
Since adrenalin is quickly absorbed in the digestive-intestinal tract, it could not be used orally and so pharmaceutical researchers looked for alternatives. At the beginning of the 20’s, a substance from a Chinese herb, ma huang [ephedra vulgris] was isolated, which was biochemically related to adrenalin and could be used orally for effectively treating asthma. This substance, called ephedrine, is still incorporated in cough syrup and mucilaginous medicine. It became widely used for the relief of bronchial spasms, but it also had a stimulating effect on the central nervous system. During the 30’s, a synthetic variation called amphetamine was finally developed.
A new system of inhaling amphetamine gave relief to asthma symptoms. This anti-asthma substance, called benzedrine, was quickly recognized as a central stimulant which produced an effect similar to cocaine, at this time labeled in the U.S. and Europe as a narcotic. Thus was founded a cheap cocaine alternative as the benzedrine inhalers needed no prescription and the contents could simply be sold over the counter.
Ritalin Has an Effect Similar to That of Cocaine
In medical publications at the end of the 30’s, it was described that the use of amphetamine had the effect of an increase in psycho-motor capabilities without the danger of dependence, even with long term use. Cocaine and amphetamines have different chemical structures, but identical physical stimulation effects like, heightened wakefulness and euphoria, suppression of hunger, and under certain conditions, psychosis of a certain type. Subjectively, the effect of the central stimulants is labeled as providing a feeling of energy, power and a clear mind. Objectively, the limited suppression of fatigue and the accelerated physical and mental endurance has been proven in numerous tests. As a result of the attributed euphoria, “cool” performance, and appetite suppression, amphetamines were the most prescribed medication during the 70’s, even though the potential for misuse was known from the beginning.
During the Second World War, military pilots from all countries consumed amphetamines for combat endurance, and following the war, amphetamine epidemics developed in the USA, Japan, and Sweden. During the 60’s, drug users in San Francisco discovered that the euphoric effects of amphetamines could be greatly increased when intravenously injected, but were followed inevitably by sudden and deep depression phases.
However, the higher the overall feeling of pleasure attained, the deeper the depression was afterwards. The fast developing amphetamine tolerance could, as with all narcotics, only be compensated with higher and higher doses and the habitual high doses actuated the compulsive longing for the stuff, the classic drug dependency scenario.
These circumstances finally resulted in making amphetamine and its derivatives, lawfully illegal narcotics. The only clinical indication for allowing medication with amphetamine derivatives such as anphetaminil=AN1, fenetyllin=captagon, methylphenidat=ritalin and dextroamphetamine, to be used are for treating narcolepsy (sleep disorder), eating addiction (pathological gluttony e.g. after brain damage), and for hyper kinetic symptoms during childhood and teenage years.
The Mechanism of Amphetamine in the Central Nervous System
From the extreme results of amphetamine use (deep depression, paranoia, hallucinatory psychosis, and excessive appetite suppression, with gross retardation), one can induce which neurotransmitter function within the brain neurons are influenced by amphetamine and its derivatives. Because of the effects of amphetamines on the adrenaline receptors in the bronchial branches of asthmatics, it was assumed that in brain cells, analogously, the structurally related neurotransmitters noradrenaline would be increasingly released.
Adrenaline and noradrenaline operate as messengers of the sympathetic part of the autonomous nervous system, partially across the same post synaptic receptors for the functioning of inner organs like the bronchi, heart, stomach, intestines, etc. Since neurons play a dominant role in the brain via noradrenaline, the main function of the amphetamines as central stimulators had to originate via noradrenagic synapses.
During the 60’s researchers could experimentally demonstrate precisely, with a brain map, with certain color techniques and with brain parcels, the location of the noradrenagic neurons, the pathway of their axions and dendrites which were leading to other brain areas. The result was astounding and unparalleled at the same time: most of the noradrenaline neurons in the brain were concentrated in the brain stem in a comparatively small nucleus with about 3,000 neurons within the so called “blue nucleus” (locus coeruleus). These few neurons nevertheless send out axions over long stretches into other brain areas and into the bone marrow.
Across this giant spiderweb of nerve fibers, the noradrenaline neurons control many billions of other neurons in the brain stem via innumerable branches for the control of the general activities (i.e. sleeping, awakening, reflex stimulation of the bone marrow) in the thinking part of the cerebral cortex, in the hypothalamus as the controlling organ for hormone synthesis, also in the cerebellum as the organ for small motor movements, in the bone marrow for the regulation of arm and leg movement and muscle tension due to synaptic action, but also very much in the limbic system (lat. limbus- border).
The limbic system is a structure in the brain which, on an evolutionary basis, is much older than the cerebral cortex and is localized in a circular form below it.
The limbic system with its multitude of brain nuclei, which are profusely connected with noradrenagic neurons, is deemed the part of the brain that deals with emotions.
During the 70’s, brain researchers could demonstrate, through radioactive tracing of neurotransmitters, the effects of exchange with the specific receptors on the postsynaptic membranes. The results showed that amphetamines, because of their similarity in structure, will push the noradrenalin out of the bubble-like structures in which it is stored, after its synthesis in the presynaptic nerve endings. The result is that more noradrenaline molecules, with their specific receptors, have a reciprocal effect and release in the post-induced, postsynaptic neurons, a lasting effect.
Normally, the noradrenalin neurons in the blue nucleus liberate their messengers across billions of axion branches when they are induced to fire through environmental factors of emotions from the inner world of the brain which causes an emotional agitation under the influence of amphetamines. The noradrenalin receptors are on constant alert, independent of outer or inner emotions. This process explains not only the process of hyper – alertness and the ability for concentration in the cerebral cortex, but also the feeling of euphoria connected to the limbic system and the increased coordination of muscle activity. One also understands better the characteristic “coolness” of amphetamine and cocaine users, since they feel independent of inner and outer emotional changes.
Cocaine has a somewhat different mechanism but which also applies in a lesser degree to amphetamines. It impedes the resumption of noradrenalin after contact with the post-synaptic receptors in the parasynaptic nerve endings, which also increase the length and strength of the noradrenalin.
Pharmaceutical substances which are effective for certain forms of depression also impede the resumption, respectively the decomposition of noradrenalin, in the presynaptic nerve endings. That is the reason why psychiatrists have prescribed amphetamines to depressive patients. On a short term basis there is an improvement, followed by tolerance development which requires higher doses, which then leads to the typical withdrawal symptoms when the medication is stopped. The tolerance creation is explainable because of the decrease of sensitivity of the receptors (and probably also a decrease of the number of receptors) on account of the continuous effect of the noradrenalin molecules. These receptors become “immune”, which explains the dramatic depressive collapse (crashing) following an amphetamine high.
Amphetamine and cocaine influence an increase in the curbing of take-up of noradrenalin, and at the same time they influence the neurotransmitters dopamine and serotonin. The stronghold of dopamine neurons is in the “black nucleus”(substantia negra) in the brain stem. From there, long axions lead to the so-called striated bodied coordination center (corpus striatum), which is responsible for the movement of arms and legs.
Psychosis Mimicking Schizophrenia
The disturbances and degeneration of this nerve system leads to the characteristic symptoms of rigidity, decreased mobility and of tremor with Parkinsons disease. From an area next to the “black nucleus”, a dopamine like nerve trail with branches, moves to the different parts of the limbic system as well as to the oldest part of the cerebrum, the gyrus cinguli, and to the youngest structure of the frontal cerebrum {cortex frontalis}. Important parts of this dopamine stimulated cerebrum (mesolimbic dopamine system) are labeled as the “reward system”, because research with animals led us to assume that all narcotics producing euphoric effects, including amphetamines and cocaine, increase the release and respectively, the curbing of resumption or decrease of dopamine.
Since pharmaceutical substances (neuroleptica) from the schizophrenic arena are effective with psychosis, since they block specific dopamine receptors, one assumes vice versa, that amphetamines and cocaine can generate a schizophrenic like psychosis, because of the over activation of dopamine, dependent on doses and duration.
The amphetamine and cocaine psychosis differentiate themselves from the organic, physically originated psychosis, like the delirium of alcoholism or when the cerebrum is organically damaged by a tumor, through an over active condition, without disturbing consciousness. Beyond that there are other congruent symptoms with schizophrenic, like psychoses.
The afflicted experience acoustic, sometimes optic hallucinations, and feel a certain suspicion, which can develop into feelings of delusion of self. This clouds the interpretation of events and information in respect to one’s self and can lead to full-fledged psychosis, and the impression of a hostile conspiracy. At times, these congruent symptoms have led to the faulty diagnosis of schizophrenia, where amphetamine and cocaine use were present but not known to the clinician. A specific form of hallucination with amphetamine and cocaine psychosis is the tactile hallucination, which is seldom found with schizophrenia. It manifests as a disorder where the drug user experiences the sensation of crawling insects, worms, and other animals on their skin.
The immediate effect, when blocking the dopamine receptors with the help of anti schizophrenic neuroleptica in the case of amphetamine psychosis, shows that the short and long term effects of amphetamine consumption is indeed activated, not only through over stimulation of the noradrenalin receptor, but also through the over stimulation of the dopamine receptor. On the contrary, patients have shown within a short time period, heavy psychotic reactions when given small amphetamine doses, after the paranoid and non-paranoid schizophrenic symptoms had subsided. It is assumed, that by blocking the dopamine receptors with neuroleptica, the receptors are over-sensitized (up regulated), while other specific dopamine receptors are down regulated with long-term amphetamine therapy during childhood and teen years, which creates a disposition for depression and dependency in later years. Of all the important psycho-pharmaceuticals, amphetamine, and cocaine, have the strongest selective effects on the mesolimbic dopamine energetic reward system. Amphetamine also release the neurotransmitter serotonin, which comes from the amino acid tryptophan, from the reservoir in the presynaptic nerve endings. All of the serotonin nerve channel systems in the brain originate from a group of nuclei in the brain stem (raphe-nuclei) and ascend to higher centers. The axions of the serotonin neurons branch out over the whole brain but are especially interlocked tightly within the limbic system. The serotonin neuron system is seen more as a “listless system”. The appetite and growth depressant effects of amphetamines are associated with the over activation of the serotonin receptors. A deficient activation of the serotonin receptors is instrumental with certain forms of depression.
Depressive individuals with too little serotonin receptor activation often attempt serious, especially violent, suicide attempts or can be impulsively violent against others. Long-term amphetamine use can therefore, lead to a tendency for violence against self or others because of the over activation of the serotonin receptors, thereby enhancing a desensitizing of the down regulating receptors.
The Working Mechanisms of Amphetamine in the Vegetative Nervous System
Along with the desired effect from Benzedrine inhalation, dilation of the bronchi in the asthmatic patients, amphetamine also affects the adrenergic receptors in the synapses in the vegetative nervous system. This system is connected, via centers in the spine, in both directions with the central nervous system, and among other things, the hypothalamus-hypo physical system, the limbic system up to the cerebral cortex. From the spinal centers in the chest and pelvis, the nerves of the sympathetic system cross ganglia, which were redirected to noradrenergic nerve fibers, to the synapses of the inner organs.
In these sympathetic nerve fibers, amphetamines also cause increased expulsion of the neurotransmitter, noradrenaline into the synaptic crevices. The consequence is an increased stimulation of the specific membrane of the receptors which, over a long time, can be constantly overactive or hampered. For example, the heart muscles cells are accelerated and in response, the heart’s pumping and beating frequencies increases. This turbo effect nevertheless leads to oxidation, causing a lasting burden on the heart muscle cells.
The sympathetic and the counter action of the parasympathetic system are, in a neuro and anatomical sense, separate parts of the vegetative nervous system, but they work in a polar dynamic way organically in the inner organs (graphic 9) . The balance of this constant synergy is disturbed in many ways on account of the over activation of the sympathetic system by long-term amphetamine therapy.
A specific sympathetic nerve channel between the vegetative centers and the adrenals directly stimulates the release of noradrenaline and adrenaline from cells of the adrenal marrow into the blood stream when under stress. This vital cell system, influenced by amphetamines and under stress from the hormones adrenaline and noradrenaline, together with the whole metabolism and hormone and immune systems, are compromised. The adrenergic cells of the adrenal marrow are stimulated simultaneously by cortisol that formed in the adrenal cortex.
Cortisol is the final hormone from the stress cycle of the hypothalamus-pituitary-adrenal axis. This axis is also influenced by the amphetamine over activation, via the noradrenagic, dopamine and serotonin agitation of the limbic system. In this scenario the frontal pituitary excretes cortisol stimulating ACTH hormone into the blood stream, which stimulates cortisol synthesis in the adrenals. The elevated cortisol table has a stress reducing effect on the hypothalamus which acts like a control valve to prevent backflow.
This negative backward coupling can be disturbed by permanent stress. It is the opinion of today’s psychiatrists that nearly all depressive episodes are caused by stress, which blocks the cortisol. Since most of the anti -depression drugs, like amphetamine, elevate noradrenaline and serotonin in the brain synapses, the hyper kinetic syndrome and the attention deficit can be seen as stressors and the positive amphetamine effect in the beginning can be seen as a stress reducing factor. The relationship between the cortisol hormone and the adrenal receptors in the brain or between the inner organs in the periphery of the brain is, in any case, much more complicated. Since there are different adrenal recepto rs (alpha and beta receptors) and a constantly elevated cortisol level mainly sensitizes the beta receptors and increases their numbers, the signaling path of the beta receptors is more strongly activated within the cell. The relationship between the signal path via cyclical adenosinmonophosphate (cAMP) and the one mediated through the cyclical guanosinmonophosphate (cGMP) shifts in favor of the signal path of cAMP.
Imbalance of Cell Metabolism
What transpires is an imbalance in the cell metabolism and the synthesis of cell energy. The noradrenaline-adrenaline supply, elevated by amphetamine, also stimulates the alpha receptors plus the couples signal path of cGMP. The balance, decisive for the bio-energetic and biochemical cell work, can be reinstated. With too high a dosage or too long a term of amphetamine use, the receptors respond by desensitizing, (down regulation). The dosage then needs to be increased to balance the decreasing effect because otherwise, the inner and outer stressors are experienced even more. Nevertheless the dosage has been significantly limited because of undesirable side effects and because of the liberation of nonadrenal message material at the same time.
In the vegetative nerve system, in contrast to the central nervous system, dopamine plays a role only as a precursor for the synthesis of noradrenaline and adrenaline, apart from some blood gradient of the intestines and kidneys. When influenced by amphetamine, the messenger material which was synthesized from amino acids, for example serotonin, is largely liberated from intestinal mucus membrane cells and blood cells. Quantitatively, serotonin formation in the stomach and intestinal areas is higher than it is in the brain, so amphetamine overstimulation of the serotonergic receptors, due to medication and certain antidepressive substances (serotonin uptake-downgrade), can spark stomach and intestinal disturbances, even cause intestinal bleeding. Serotonin also affects, (according to organ type retarding or increasing), the smooth musculature of blood gradients in the brain (migraine), the lungs, the kidneys, the skeletal muscles, the smooth muscles of the bronchi, of the stomach intestinal tract, the uterus, and others, as well as stimulating the heart activity.
Permanent Ritalin Therapy Consequences and Alternatives
The exceptional diversity of effecting the psychic organ and cell functions with amphetamines should demonstrate to the medical and lay person that the effects of a long term Ritalin treatment are more harmful than the desired positive therapeutic effects.
Yet, the short-term effect of Ritalin with hyper active children and teens, who apparently cannot sit still or concentrate on a specific task, is highly astonishing. Following the first oral doses of Ritalin, starting out with 510 mg, the child quiets down within a few hours and the hyper active syndrome decreases quickly. The afflicted can concentrate again rather than run around in constant motion. They overcome their apparent learning disability and sometimes even seem overly conscientious. The over burdened parents and teachers are relieved that the afflicted child or teen is no longer labeled as a disturbance.
The justified concern that normal or outstanding children and teens having ADHD could turn into social outsiders and could develop negative self images, the side effects of Ritalin, which in reality are synergistic effects, seem to be acceptable. One hopes that the symptoms, in time, will improve spontaneously and that the Ritalin therapy will no longer be necessary. This expectation, nevertheless, is false.
As with all amphetamines, there is a reduction in effectiveness over time, because the effective dosage has to overcome the threshold value for the activation of the adrenal alpha-receptors. The permanent stimulation of these receptors, caused by Ritalin, also activates a desensitizing effect, as a counter regulation of the receptors. The therapeutic dose has to be increased and the dependency potential develops which involves the noradrenaline, dopamine, and serotonin receptors as well as their coupled intracellular signal pathways and the synthesis of the cell energy. Besides that, the danger exists with higher Ritalin doses that the neurotransmitter reservoirs don’t replenish fast enough because Ritalin forces a sudden drainage. The result can be unexpected psycho-social and organic slips .
A vicious cycle develops. If the long term Ritalin therapy is reduced or discontinued because of intolerable side effects e.g., sleep disorder, loss of appetite, stunted growth, rapid heart beating, or irregular heart beating, elevated blood pressure, gastro-intestinal disorders, hallucinations etc., the original ADHD (ADS) symptoms and withdrawal symptoms with an individual symptoms can appear even stronger.
To psychiatrists specializing in child and teen therapy, the Ritalin effect with hyper active children and teens often seems paradoxical when compared to the effect that amphetamine has on grownups. In reality, the Ritalin effect does not dampen the psychic and vegetative activities, but raises the wakefulness, like amphetamine does with grownups, and puts the postsynaptic noradrenalin receptors into a permanent alarm situation. The medical effect has to be understood analogically like a continuous emotional stimulation due to an over-irritation of the surroundings or the inner turmoils of the afflicted. The continuous central stimulation therefore, over-rides the actual cause of ADD and hyperactive restlessness, and can heal it.
Ritalin is a Doping Medication Not a Healing Medication
Inevitably the question arises whether the cause of ADD is indeed a deficit of the noradrenalin or due to the different sensitivities of the noradrenergic sub-receptors when under normal noradrenalin release. The fact is that when an increase of noradrenalin, induced by Ritalin, takes place, enough noradrenalin is at hand and the noradrenalin receptors are quickly and lastingly agitated; this underlines the fact that with hyperactive children, the alpha receptors, under stress with normal noradrenalin output, are not sufficiently stimulated and the dopamine psycho-motor synapses are not sufficiently counter stimulated. The central stimulation of the noradrenergic alpha receptors seem to be, at first glance, the means for stimulating the wakefulness and attention controlling brain area during therapeutic practice. Long tern Ritalin therapy proves to interfere enormously with personality development and physical maturity during childhood and teen years, with highly risky long-term consequences as seen by the above explanation.
Ritalin and Narcolepsy
In the same context, the therapeutic experiences are of special interest in regards to the legal use of Ritalin for the treatment of narcolepsy (greek. Narke-paralyse, leptein-seize). With this relatively seldom-occurring ailment, emotional stress often induces irresistible sleepiness, opposite to a normal, heightened wakefulness. The afflicted fall asleep spontaneously during the day for about 15 minutes while walking or standing up, but can be awakened.
The narcoleptic symptoms can be linked to a loss of muscular tension, so called sleep paralysis, going to sleep and waking up, and to acoustic and optical hallucinations. According to psychiatrists, the origin seems unknown, similar to the hyperactive syndrome of ADHD.
Those with narcolepsy are most often treated with Ritalin as Ritalin counteracts the tendency to fall asleep. But long term Ritalin therapy, on a regular basis, has created a dependency potential. In order to maintain a balanced effect, the required dosage has to be increased and, once the medication is stopped, withdrawal symptoms appear.
Since serotonin is involved with sleep control (non-REM-sleep phase), an increased dopamine level in the limbic system can produce hallucinations and, since noradrenalin receptor activation regulates muscle tension, the symptoms of narcolepsy can also start intermittently. Relatively strong stimulation of the serotonin and dopamine receptors and a weak counter-control by the noradrenergic neurons in the general activation system of the brain stem ensues.
Therapeutic Alternatives to Ritalin
With the search for therapeutic alternatives for narcoleptic patients, the dependency producing effects of Ritalin therapy have been replaced with the natural amino acid, tyrosine. Since tyrosine is a precursor of the synthesis chain of DOPA-dopamine-noradrenalin-adrenalin (see graph 4) , the disadvantage of long term Ritalin stimulation can be circumvented. Because of the increased tyrosine, more noradrenalin can be synthesized and stored. If needed during emotional irritation of the noradrenergic neurons within the “blue nucleus” of the brain stem, it can be released and the effects of the dopamine and serotonin neurons can therefore, be better counter-controlled.
The advantage is that neither the beta nor alpha receptors of the noradrenergic neuron system, nor the dopamine and serotonin receptors, are exposed to constant, permanent stimulation through Ritalin and amphetamines with all their deleterious effects on the central and vegetative nervous system. The increased reservoir of noradrenalin can be tapped when there is a recall in a state of emotional agitation in the noradrenergic nerve endings.
From the experience with simple tyrosine stimulation instead of long-term Ritalin stimulation, the alternative therapy principle for children and teens with ADD and ADHD can be derived from an orthomolecular therapy principle. In clinical studies, tyrosine applications have shown to produce stress-reducing effects. The recommended daily oral dose of tyrosine is 50-100 mg per 1 kg of bodyweight.
Tyrosine is also the starter molecule for the synthesis of the thyroid hormone (thyromine). Under stress conditions the free thyronine (T3), in relationship to the inactive reverse thyronine (rT3), respectively to the thyronine which is tied to a protein, is decreased. The T3 content is nonetheless essential for the synthesis of the universal energy carrying molecule adensintriphosphate (ATP) within the breathing cells of the mitochondria. n the adrenergic stimulated neurons the ATP requirement is increased, since the ionic in and out flow, plus the secondary signal pathways, are energy dependent.
T3-thyronine deficiency can also produce psycho-motor unrest and lack of concentration.
Thyronine supplies can be increased through an oral intake of folic acid (500-5000 micrograms daily for 3-6 months). Tyrosine synthesis from the essential amino acid phenylalanine, taken in through food, requires, among other things, the essential coenzyme, tetrahydrobiopterin (BH4), which becomes available from the metabolism of the folic acid. Folic acid is also necessary for the synthesis of ATP, cAMP and cGMP. Folic acid deficiency is the most prominent vitamin deficiency in Europe and the USA.
For the balance of the neurotransmitters, the specific regulation of the receptor activities, the harmonizing of the post-synaptic signal paths and the availability of cell energy 1 because of the mitochondrial cell symbioses the modulation of protaglandins which requires the uptake of enough fatty acids is essential. The prostaglandins belong to the large family of cell hormones which are formed enzymatically from the essential fatty acid arachidon, (split from phospholipids in the cell membrane). Under stress, the prostaglandin PGE2 is elevated, which raises the synthesis of camp, disadvantageous to cGMP because it restricts synthesis of the gaseous forming bio-regulator, nitrogen monoxide (NO). (see Kremer, H.:, “The Quiet Revolution of Cancer and AIDS- Medicine”. Ehlers Publishers, Wolfratshausen, December 2001).
PGE2 can be best curbed by omega 3/omega 6 fatty acids (best in the ratio 3:1). Recommended is the regular consumption of cold water fish, better yet, the daily intake of micro algae, e.g. AFA bluegreen algae, in the form of tablets or powder daily. This medicine is obtained from the micro algae Aphanizomenon flos-aquae which is free of contamination and also has a high content of essential fatty acids, minerals, and trace elements, vitamins and protein. Micro algae are at the beginning of the maritime food chain and are the stem cells of the plants. They gain the energy for their biosynthesis of carbohydrates directly from the sunlight (high bio photon content) and offer their ATP energy molecules just like the human cell symbiosis mainly via the respiratory chain of the mitochondria. They store and synthesize independently most of the essential micro and macro energy material for the human metabolism.
These indications for the possibilities of a rationally and biologically balanced therapy at a time when disparities appear in the neurotransmitter family and the neural cell energy because of inner and outer stress, shall serve as examples, but are not covered to their maximum. What counts is an understanding of today’s bio-energetic and biochemical procedures in the brain in order to weigh the long-term consequences without a long term Ritalin therapy and support a psychotherapeutic and social pedagogical therapy.
Pressing Questions for Doctors Prescribing Ritalin
Ritalin may only be prescribed by licensed medical doctors. The more than 40,000 accepted long-term Ritalin therapies are therefore, all to be attributed to medical doctors.
The following recommendation for those studying to become MD’s is certainly correct and necessary: “treatment without drugs have superiority (Training for parents, behavior modification)”
1. Why do recommendations for substance therapy of exclusively dextroamphetamin and methylphenidat {Ritalin}, during lectures for the medical examination, predominate?
2. Why is there no discussion of alternatives? {Karov, Th.Lang, R.: General and specific Pharmacology and Toxicology}. Prof. Lehmkuhl and his colleagues at the psychiatric department for children and teens in Koeln concluded: It is important to maintain a continuous control during treatment. Because treatment can only be justified when positive effects can be demonstrated.” {Schubert,J.et.al.a.a.O.}.
3.What do you understand by “positive therapy effects” during the treatment of an individuals long term doping?
4. What are the alternatives when the therapeutic effects can no longer be declared as positive?
5. How do you measure these positive effects, since there is not enough data which could serve as qualitatively safe for the therapy and there is not sufficient data from epidemiological research?
6. Why are there no long-term studies since Ritalin has been prescribed for 50 years? Because the results did not show any positive therapeutical effects?
7. Do you have to harm thousands of children and teens physically and psychically in order to demonstrate the side effects of a long-term Ritalin therapy, which according to present day knowledge, can be deduced by logic without a long term study?
8. Would the more than 40,000 children and teens which are on constant Ritalin doping have to participate in a detoxification program? Or is the highest medical principle not applicable anymore which states: nil nocere {never harm} in regards to hyperactive children and teens? Or do the prescribing doctors simply not know what they are doing? Or do they simply not want to know 40,000 times and more , because the preeminence of parental training and behavior modification is too time and cost consuming within a therapeutic reality?
8. Would an education and behavior therapy for prescribing doctors not be quite as urgent? Or do the law makers have to stop Ritalin from being prescribed so that a new way of thinking can develop?
10. Is it responsible in regards to medical ethics when it has been postulated that the number of hyperactive children and teens requiring Ritalin is supposed to be 4 times higher than the ones on long term therapy and therefor no lack of inappropriate treatment exists in Germany despite the fact that a long term Ritalin therapy might not be indicated?
